Low White Blood Cell Count Pancreatic Cancer – A novel Antrodia cinnamomea extract reduced cancer stemness-like phenotype changes and resensitized KRAS-mutant colorectal cancer through the MicroRNA-27a pathway
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- 1 Low White Blood Cell Count Pancreatic Cancer
- 2 Multiomic Characterization Of Pancreatic Cancer Associated Macrophage Polarization Reveals Deregulated Metabolic Programs Driven By The Gm Csf–pi3k Pathway
- 3 Values Of Applying White Blood Cell Counts In The Prognostic Evaluation Of Resectable Colorectal Cancer
- 4 Natural Killer T Cell Immunotherapy Combined With Il 15 Expressing Oncolytic Virotherapy And Pd 1 Blockade Mediates Pancreatic Tumor Regression
Low White Blood Cell Count Pancreatic Cancer
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Multiomic Characterization Of Pancreatic Cancer Associated Macrophage Polarization Reveals Deregulated Metabolic Programs Driven By The Gm Csf–pi3k Pathway
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By Verena Martini Verena Martini Scilit Preprints.org Google Scholar View Publications 1 , Sylvia Timme-Bronsert Sylvia Timme-Bronsert Scilit Preprints.org Google Scholar View Publications 2 , Stefan Fichtner-Feigl Stefan Fichtner-Feigl Scilit Preprints.org Google Scholar View Publications , 3 , Jens Hoeppner Jens Hoeppner Scilit Preprints.org Google Scholar View Publications 1, 3 and Birte Kulemann Birte Kulemann Scilit Preprints.org Google Scholar View Publications 1, *
Values Of Applying White Blood Cell Counts In The Prognostic Evaluation Of Resectable Colorectal Cancer
Department of General and Visceral Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
Initial submission received: 22 September 2019 / Revised: 22 October 2019 / Accepted: 24 October 2019 / Published: 26 October 2019
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and Europe; there are no early symptoms or screening, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. During the last twenty years (1999–2019), 140 articles have included the keywords “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis”. The articles evaluated the use of CTCs as prognostic markers and their correlation with survival in pancreatic ductal adenocarcinoma (PDAC). In the 17 articles finally selected, CTC detection rates varied widely between different enrichment methodologies and ranged from 11% to 92%; most studies used antigen-dependent CellSearch
System for CTC detection. Fifteen reviewed studies showed a correlation between the presence of CTC and worse overall survival. The heterogeneity of CTC detection methods and the lack of consistent results prevent comparison between the evaluated studies. However, CTCs can be detected in pancreatic cancer and hold promise as an early detection tool. Larger studies are needed to confirm CTCs as valid biomarkers for pancreatic cancer.
Pancreatic Cancer: Pharmacologic Management
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States and Europe [1, 2]. Its incidence is almost equal to mortality, with a five-year survival rate of <6% , and it is likely to be the second leading cause of cancer-related death in 2030, surpassing breast and colorectal cancer . The disease is often detected in metastatic stages, reflecting its late diagnosis and aggressive biology. Early symptoms are rare and most patients initially experience mild symptoms such as abdominal discomfort, back pain, fatigue and weight loss. Distant organ metastases are the end result of hematogenous spread of cancer cells, with which about 80% of patients are diagnosed; There is currently no adequate screening scheme for early detection of PDAC.
Currently, most treatment decisions are based on tumor stage as assessed by cross-sectional imaging and endoscopic tumor biopsy. Computed tomography (CT) and magnetic resonance imaging (MRI) are widely used, but MRI has higher diagnostic sensitivity and accuracy . Approximately one-fifth of patients are “low-stage” because metastatic disease is often only visible at operative examination .
To date, only serum CA19.9 has been routinely used as a noninvasive blood-based biomarker in PDAC. However, it does not act as a diagnostic tool alone, but high CA19.9 levels often indicate advanced tumors . A concern with this biomarker is that elevated expression of CA19.9 may occur in a variety of benign (pancreatitis, acute cholangitis, and cirrhosis) and malignant (colorectal cancer, gastric cancer, bladder cancer, and uterine squamous cell carcinoma) diseases in addition to PDAC. , resulting in its non-specificity. In addition, CA19.9 is not expressed in approximately 10% of the Caucasian population, and only 65% of patients with resectable PDAC have elevated levels of CA19.9 . CEA also serves as a biomarker, although it has some of the disadvantages of CA19.9 and also lacks specificity.
Other blood-based biomarkers are not routinely used or have not yet entered clinical practice. Liquid biopsies such as circulating tumor DNA (ctDNA), exosomes, plasma proteomics, and circulating tumor cells (CTCs) have now been studied for over a decade with encouraging results that are partially discussed in this review; however, there are no clear clinical recommendations for patients with PDAC.
Pb Pretargeted Theranostics For Pancreatic Cancer
Routine treatment of resectable PDAC involves complete resection of the tumor followed by heterogeneous chemotherapy. Gemcitabine is routinely used as a first-line treatment with survival rates of several months . Historically, neoadjuvant regimens have shown efficacy. Without randomized trials, however, physicians stick to initial surgery in resectable cases . Recently, some new adjuvant chemotherapeutic protocols have been introduced into clinical practice. Gemcitabine, FOLFIRINOX and paclitaxel have been used as part of clinical trials, and the combination of nab-paclitaxel and gemcitabine has recently been shown to increase overall survival in metastatic pancreatic carcinoma compared to gemcitabine alone . The same results have been documented for gemcitabine and FOLFIRINOX  with higher toxicity and more side effects in the metastatic FOLFIRINOX group. The current PANACHE01 trial is evaluating the efficacy of two neoadjuvant chemotherapy regimens, FOLFOX and mFOLFIRINOX, compared with standard-of-care surgery followed by adjuvant gemcitabine in resectable PDAC .
Limited diagnostic capabilities as well as complex and narrow treatment options emphasize the need for prognostic and predictive biomarkers. A prognostic biomarker can provide insight into patient outcomes regardless of treatment received. This biomarker can provide an estimate of survival, time to disease progression, or type of progression. In contrast, a predictive biomarker can identify a subset of patients who would benefit from a particular cancer treatment, and thus can guide treatment decisions. An ideal biomarker is noninvasive, repeatedly accessible, reasonably priced, and easy to analyze.
In this review, we provide an overview of the current literature on pancreatic cancer CTCs in the clinical context. We focus on studies evaluating the clinical applications of CTCs in PDAC patients. We also discuss the problems of inhomogeneous CTC isolation and analysis and highlight possible research perspectives.
Patients with pancreatic cancer often present with nonspecific symptoms such as weight loss, back pain, abdominal pain, and fatigue. Cross-sectional imaging, endoscopy, serum biomarkers, and histological biopsies are currently potential tools used in clinical routines to diagnose pancreatic cancer [ 12 , 13 ]. When imaging is inconclusive and prior to oncologic treatment, endoscopic ultrasound techniques are combined with fine-needle aspiration to obtain a biopsy and confirm the tumor diagnosis. Due to the anatomical location of the pancreas, this procedure is technically difficult and has many complications. In addition, false-negative results occur in many cases due to cannulation of stromal cells, which constitute the majority of the tumor mass . This results in repeated invasive biopsies with the risk of tumor spread and post-interventional complications. In some cases, laparoscopic or even open surgery is required to obtain a tumor sample to confirm the diagnosis of pancreatic cancer. Currently, there are no specific screening tests available for pancreatic cancer.
Natural Killer T Cell Immunotherapy Combined With Il 15 Expressing Oncolytic Virotherapy And Pd 1 Blockade Mediates Pancreatic Tumor Regression
The causes of pancreatic cancer (PC) are multifactorial and diverse. High-risk groups include patients with a positive family history of PC, hereditary PC, familial atypical multiple mole melanoma (p16 mutation), cystic fibrosis, Peutz-Jeghers syndrome, Lynch syndrome, and HBOC (BRCA1/BRCA2 mutation). Risk factors for the development of PC are advanced age, male gender, obesity, smoking, pancreatitis and diabetes mellitus. New diabetes is considered a risk factor for PC, but whether it is a cause or a consequence of PC is still unclear [4, 7, 15].
PDAC is characterized by several genetic variants associated with tumor formation and progression. Point mutations in the Kirsten rat sarcoma virus oncogene homolog (KRAS) gene occur in more than 90% of tumors [ 7 , 16 , 17 , 18 ] and are thought to be an early event in tumorigenesis. Other driver mutations such as TP53, p16 and SMAD4 are also commonly found in PDAC samples [15, 16]. Recently, a “three-step procedure” theory of carcinogenesis has been introduced for PDAC. These steps are as follows: First, initiation
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